Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

Subjects were enrolled from 04 Feb to 05 Nov 2008 at 19 centers in 5 countries (Germany, France, United Kingdom, Italy and Poland).

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

Of the 89 subjects enrolled, 83 were treated with the study drug. Safety population = 83 subjects who took at least one dose of study drug and had any data after baseline. Intent to treat population = 67 subjects treated with the study drug who had at least one efficacy evaluation after baseline.

Reporting Groups

Description

Sorafenib (Nexavar, BAY43-9006)

Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

No text entered.

Reporting Groups

Description

Sorafenib (Nexavar, BAY43-9006)

Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.

Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst). Status 0 = fully active; Status 1 = restricted strenuous activity, ambulatory and able to carry out work of a light or sedentary nature

[2]

Categorized information on tumor size, lymph node involvement and metastases. Stages I-IV. The higher the stage, the more advanced cancer.

Best Response - mITT (Modified Intent-to-treat) Population [ Time Frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. ]

Tumor Response - ITT (Intent to Treat) Population [ Time Frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. ]

Pharmacokinetics (PK) Analysis – Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) [ Time Frame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8 and 10 hours post-dose. ]

Pharmacokinetics (PK) Analysis – Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) [ Time Frame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose. ]

Pharmacokinetics (PK) Analysis – Maximum Observed Concentration in Plasma (Cmax) [ Time Frame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose. ]

Pharmacokinetics (PK) Analysis – Time to Maximum Concentration (Tmax) [ Time Frame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose. ]

Progression-free Survival (PFS) [ Time Frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. ]

Time to Progression (TTP) [ Time Frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. ]

Tumor Response - mITT Population [ Time Frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. ]

Disease Control - mITT Population [ Time Frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. ]

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release
and can embargo communications regarding trial results for a period that is less than or equal to 60 days.
The sponsor cannot require changes to the communication and cannot extend the embargo.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release
and can embargo communications regarding trial results for a period that is more than 60 days but less than
or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:
The Principal Investigator (PI) can publish results following completion of study. The PI must discuss a publication with Bayer prior to release&obtain written consent to proceed. The Investigator must send a draft to Bayer at least 30d in advance of submission to obtain approval. Any submission to Bayer will be reviewed w/o unreasonable delay&approval not be withheld unreasonably. In difference of opinion publication will be discussed.